USPTO Patents Application 09978191

DO NOT ENTER: /C.S./

The opinion in support of the decision being entered today was not written
for publication and is not binding precedent of the Board.

UNITED STATES PATENT AND TRADEMARK OFFICE

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES

Ex parte AUDREY GODDARD, PAUL J. GODOWSKI,
AUSTIN L. GURNEY, VICTORIA SMITH, and WILLIAM I. WOOD

Appeal 2006-1469
Application 10/123,212
Technology Center 1600

Decided: April 30, 2007

Before TONI R. SCHEINER, ERIC GRIMES, and LORA M. GREEN,
Administrative Patent Judges.

GREEN, Administrative Patent Judge.

DECISION ON APPEAL

This is a decision on appeal under 35 U.S.C. § 134 from the
examiner's final rejection of claims 72-79 and 82-84. We have jurisdiction
under 35 U.S.C. § 6(b). Claims 72 and 77 are representative of the claims
on appeal, and read as follows:

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72. An isolated polypeptide having at least 80% amino acid
sequence identity to:

(a) the amino acid sequence of the polypeptide of SEQ ID NO: 14;

(b) the amino acid sequence of the polypeptide of SEQ ID NO: 14,
lacking its associated signal peptide; or

(c) the amino acid sequence of the polypeptide encoded by the full-
length coding sequence of the cDNA deposited under ATCC accession
number 203577,

wherein the nucleic acid encoding said polypeptide is overexpressed
in colon, lung or prostate tumor cells.

77. An isolated polypeptide comprising:

(a) the amino acid sequence of the polypeptide of SEQ ID NO: 14;

(b) the amino acid sequence of the polypeptide of SEQ ID NO: 14,
lacking its associated signal peptide; or

(c) the amino acid sequence of the polypeptide encoded by the full-
length coding sequence of the cDNA deposited under ATCC accession
number 203577.

Claims 72-79 and 82-84 stand rejected under 35 U.S.C. § 101 as not
being supported by either a specific and substantial utility or a well-
established utility. Claims 72-76, 83, and 84 stand rejected under 35 U.S.C.
§ 1 12, first paragraph, as not being enabled by the specification, and claims
72-76, 83, and 84 stand rejected under 35 U.S.C. § 1 12, first paragraph, as
lacking adequate written description. Finally, 72-74, 83, and 84 stand
rejected under 35 U.S.C. § 102(e) as being anticipated by Young, 1 and
claims 72-75, 83, and 84 stand rejected under 35 U.S.C. § 102(e) as being
anticipated by Stanton. 2

We Affirm-In-Part.

' Young, US Patent No. 6,525,174 Bl, issued February 25, 2003.

2 Stanton, US Pub. No. 2002/01 10804 Al, published August 15, 2002.

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UTILITY

ISSUE

The Examiner contends that the Specification fails to establish a
specific and substantial utility or a well-established utility of the polypeptide
ofSEQ ID NO: 14.

Appellants contend that Example 30 presents microarray data
demonstrating that the polypeptide of SEQ ID NO: 14 is a diagnostic marker
for colon, lung, and prostate tumors.

The issue is thus whether the microarray data presented in Example
30 of the Specification is sufficient to establish a specific and substantial
utility or a well-established utility for the polypeptide of SEQ ID NO: 14?

FACTS

The Examiner rejected claims 72-79 and 82-84 under 35 U.S.C. § 101
as not being supported by either a specific and substantial asserted utility or
a well-established utility (Answer 4).

The Examiner notes that the Specification discloses the polypeptide of
SEQ ID NO: 14 (PRO 1 866), the nucleic acid sequence encoding it (SEQ ID
NO: 13), as well as antibodies against the polypeptide. (Id.)

As to a well-established utility, the Examiner asserts that the prior art
does not demonstrate that the polypeptide of SEQ ID NO: 14, the nucleic
acid encoding the polypeptide or an antibody that binds to the polypeptide,
has "any well-established biological functions or any physiological
significance." (Mat 4-5.)

Next, as to a specific and substantial utility, the Examiner references
Table 8 of the Specification, which states that the polypeptide is

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significantly overexpressed in colon, lung, or prostate tumors compared to a

non-cancerous human tissue control. (Id. at 5.) The Examiner also notes

that the statement is based on a microarray analysis, which measures mRNA

levels, and not overexpression of the polypeptide of SEQ ID NO: 14 itself.

(Id.) According to the Examiner:

There is no sufficient information or experimental data
presented on whether the polypeptide or the nucleic acid of the
present invention can serve as a reliable diagnostic marker for
colon, lung or prostate tumors; there is no statistical analysis of
the expression data. Moreover, the assay does not establish a
causative link between the polypeptide (or nucleic acid) of the
present invention and colon, lung or prostate tumors. Without
such critical information, one skilled in the art would not be
able to use the molecule of the present invention as a diagnostic
marker or as a therapeutic target for treatment of colon, lung or
prostate tumors without undue experimentation. Accordingly,
the results in Table 8 obtained based upon the assay described
in Example 30 only serve as the beginning point for further
research on the biological functions or physiological
significance of the polypeptide of SEQ ID NO:[]14 or the
nucleic acid encoding the polypeptide, and does not provide a
specific and substantial utility for the present invention.

(Id. at 5-6.)

Appellants argue that patentable utility is demonstrated by Example
30 of the Specification (Br. 4). According to Appellants, Example 30
demonstrates that the gene encoding the polypeptide of PRO 1866 (SEQ ID
NO: 14) "showed significant overexpression in colon, lung, and prostate
tumors as compared to a universal normal control," demonstrating "'that the
PRO polypeptides of the present invention are useful ... as diagnostic
markers for the presence of one or more cancerous tumors (Id.)

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Appellants argue further that it is legally incorrect for the Examiner to
require specific data, statistical analysis, and further details before accepting
the utility set forth in the Specification, as the law is clear that the Examiner
must accept Appellants' assertion of utility if that assertion would be
credible to one of ordinary skill. (Id. at 4-5.)

Appellants assert that the Examiner has used an improper standard in
asserting that mRNA levels do not necessarily correlate with the protein
level and that protein levels cannot be accurately predicted from mRNA
levels. (Id. at 6.) The evidentiary standard to be used during examination is
preponderance of the evidence under the totality of the circumstances, and
thus, Appellants argue, the Examiner "must establish that it is more likely
than not that one of ordinary skill in the art would doubt the truth of the
statement of utility," which "is a much lower standard than a 'necessary'
correlation or 'accurate' prediction, and is clearly met for the invention
claim." (Id. (emphasis in original)).

Moreover, Appellants rely on the Declaration of Dr. Paul Polakis,
which states that "in general, there is a correlation between mRNA levels
and polypeptide levels." (Br. 6 (emphasis in original)). Appellants also rely
on the Declaration of Dr. Victoria Smith, which states that "microarray
analyses actually performed in my laboratory have shown that when
molecules are identified as being overexpressed in a human tumor sample of
epithelial origin relative to the 'universal normal control' 3 sample, in a
majority of cases, that molecule is also confirmed as being overexpressed in

3 The "universal" epithelial control sample is prepared by pooling non-
cancerous human tissues of epithelial origin, including liver, kidney, and
lung (Br. 12).

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the human tumor tissue sample relative to its human tissue counterpart" (Br.
6 (emphasis in original)). Appellants aver that the two declarations support
the assertion of utility in the Specification, i.e., that the PRO 1866
polypeptide (SEQ ID NO: 14) "is reasonably expected to be overexpressed in
colon, lung and prostate tumors and can be used as a cancer diagnostic
marker." (Id. at 6-7.)

The Specification is drawn to the identification and isolation of novel
DNA and to the recombinant production of polypeptides (Specification 1).

Example 30 on page 134 of the Specification is drawn to microarray
analysis to detect PRO polypeptides in cancerous tumors.

According to the Specification:

In the present example, cancerous tumors derived from
various human tissues were studied for PRO polypeptide-
encoding gene expression relative to non-cancerous human
tissue in an attempt to identify those PRO polypeptides which
are overexpressed in cancerous tumors. Two sets of
experimental data were generated. In one set, cancerous human
colon tumor tissue and matched non-cancerous human colon
tumor tissue from the same patient ("matched colon control")
were obtained and analyzed for PRO polypeptide expression
using . . . microarray technology. In the second set of data,
cancerous human tumor tissue from any of a variety of different
human tumors was obtained and compared to a "universal"
epithelial control sample which was prepared by pooling non-
cancerous human tissues of epithelial origin, including liver,
kidney, and lung. mRNA isolated from the pooled tissues
represents a mixture of expressed gene products from these
different tissues. Microarray hybridization experiments using
the pooled control samples generated a linear plot in a 2-color
analysis. The slope of the line generated in a 2-color analysis
was then used to normalize the ratios of (testxontrol detection)
within each experiment. The normalized ratios from various
experiments were then compared and used to identify clustering

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of gene expression. Thus, the pooled "universal control"
sample not only allowed effective relative gene expression
determinations in a simple 2-sample comparison, it also
allowed multi-sample comparisons across several experiments.

In the present experiments, nucleic acid probes derived
from the herein described PRO polypeptide-encoding nucleic
acid sequences were used in the creation of the microarray and
RNA from the tumor tissues listed above were used for the
hybridization thereto. A value based upon the normalized
ratio: experimental ratio was designated as a "cutoff ratio".
Only values that were above this cutoff ratio were determined
to be significant. Table 8 below shows the results of these
experiments, demonstrating that various PRO polypeptides of
the present invention are significantly overexpressed in various
human tumor tissues as compared to a non-cancerous human
tissue control. As described above, these data demonstrate that
the PRO polypeptides of the present invention are useful not
only as diagnostic markers for the presence of one or more
cancerous tumors, but also serve as therapeutic targets for the
treatment of those tumors.

{Id. at 134-35.)

As to PRO 1866, the Specification presents Table 8, which states that
PRO 1866 is overexpressed in colon tumor, prostate tumor, and lung tumor,
as compared to universal normal control. (Id. at 135.)

The Declaration of Dr. Paul Polakis, dated September 9, 2005, states
in paragraphs 4 and 5 that, based on experience with other gene transcripts
that are present in human tumor cells at significantly higher levels than in
corresponding normal human cells, it has been observed "that there is a
strong correlation between changes in the level of mRNA present in any
particular cell type and the level of protein expressed from that mRNA in
that cell type. In approximately 80% of our observations we have found that
increases in the level of a particular mRNA correlates with changes in the

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level of protein expressed from that mRNA when human tumor cells are
compared with their corresponding normal cells."

The Declaration of Dr. Victoria Smith at paragraph 5, dated
September 9, 2005, states that the comparison of mRNA expression levels in
human tumor tissues to mRNA expression levels in a sample prepared by
pooling non-cancerous human tissues of epithelial origin "is extremely
informative and provides a strong basis for the diagnostic determination of
cancer in humans."

PRINCIPLES OF LAW

The examiner bears the initial burden of showing that a claimed
invention lacks patentable utility. See In re Brana, 51 F.3d 1560, 1566, 34
USPQ2d 1436, 1441 (Fed. Cir. 1995). ("Only after the PTO provides
evidence showing that one of ordinary skill in the art would reasonably
doubt the asserted utility does the burden shift to the applicant to provide
rebuttal evidence sufficient to convince such a person of the invention's
asserted utility.").

The Court of Appeals for the Federal Circuit addressed the utility
requirement in In re Fisher, 421 F.3d 1365, 76 USPQ2d 1225 (Fed. Cir.
2005). The Fisher court interpreted Brenner v. Manson, 383 U.S. 5 19, 148
USPQ 689 (1966), as rejecting a "de minimis view of utility." 421 F.3d at
1370, 76 USPQ2d at 1229. The Fisher court held that § 101 requires a
utility that is both substantial and specific. Id. at 1371, 76 USPQ2d at 1229.
The court held that disclosing a substantial utility means "show[ing] that an
invention is useful to the public as disclosed in its current form, not that it
may prove useful at some future date after further research. Simply put, to

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satisfy the 'substantial' utility requirement, an asserted use must show that
that claimed invention has a significant and presently available benefit to the
public." Id., 76 USPQ2d at 1230.

The court held that a specific utility is "a use which is not so vague as
to be meaningless." Id. In other words, "in addition to providing a
'substantial' utility, an asserted use must show that that the claimed
invention can be used to provide a well-defined and particular benefit to the
public." Id.

ANALYSIS

We find that the microarray data presented in Example 30 of the
Specification is sufficient to establish a specific and substantial utility for the
polypeptide of SEQ ID NO: 14, and the rejection is reversed.

The microarray data demonstrates that mRNA for the PRO 1 866
polypeptide (SEQ ID NO: 14) is overexpressed in colon tumor, prostate
tumor, and lung tumor, as compared to universal normal control. Thus, the
polypeptide of SEQ ID NO: 14 has a significant and presently available
benefit to the public as a tumor marker.

We have considered the Examiner's assertions that microarray
analysis measures mRNA levels, and not overexpression of the polypeptide
of SEQ ID NO: 14 itself. As demonstrated by the Polakis and Smith
Declarations, however, there is a strong correlation between mRNA levels
and protein expression, and the Examiner has not presented any evidence
specific to the PRO 1866 polypeptide to refute that.

Finally, the use of the PRO 1866 polypeptide as a cancer marker is
sufficient to demonstrate utility, and there is no requirement that a causative

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link between the polypeptide (or nucleic acid) of the present invention and
colon, lung or prostate tumors be demonstrated.

ENABLEMENT

ISSUE

The Examiner contends that the disclosure does not enable one skilled
in the art to practice the full genus of peptides encompassed by Appellants'
claims.

Appellants contend that one skilled in the art could practice the full
scope of the claimed invention, as the skilled artisan has a sufficiently high
level of technical competence to identify sequences with at least 80%
identity to SEQ ID NO: 14, and the specification provides ample guidance
such that one of skill in the art could readily test the nucleic acid encoding a
variant polypeptide to determine whether it is overexpressed in colon, lung
or prostate tumors by the methods set forth in Example 30.

Thus, the issue is does the Specification enable one skilled in the art to
use the full scope of the PRO 1866 (SEQ ID NO: 14) variants of claim 72
without an undue amount of experimentation?

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FACTS

The Examiner rejected claims 72-76, 83, and 84 under 35 U.S.C. §
1 12, first paragraph, on the grounds that the instant disclosure does not
enable the full scope of the claimed subject matter (Answer 7). 4

As we find that Appellants do not argue the claims separately, we
focus our attention on independent claim 72. 37 C.F.R. § 41.37(c)(l)(vii)
(2006).

The Examiner made the following findings with respect to the factors
set out in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir.
1988). 5

The breadth of the claims: The Examiner notes that the claims are broad and
encompass a genus of variants of SEQ ID NO: 14 (Answer 8).
Nature of the invention and the state of the prior art The Examiner notes
that while the Specification teaches that the polypeptide of SEQ ID NO: 14 is
overexpressed in colon, lung or prostate tumors, the polypeptide "does not
have any defined biological functions or activities." (Id.)

4 The Examiner also rejected claims 72-79 and 82-84 under 35 U.S.C. § 1 12,
first paragraph, on the grounds that "since the claimed invention is not
supported by either a specific and substantial utility or a well established
utility . . ., one skilled in the art clearly would not know how to use the
claimed invention" (Answer 7). Since that rejection relies on the utility
rejection, and as we have reversed that rejection, this rejection is also
reversed.

5 The factual considerations discussed in Wands are: (1) the quantity of
experimentation necessary to practice the invention, (2) the amount of
direction or guidance presented, (3) the presence or absence of working
examples, (4) the nature of the invention, (5) the state of the prior art, (6) the
relative skill of those in the art, (7) the predictability or unpredictability of
the art, and (8) the breadth of the claims.

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The Examiner notes further that two variants of the polypeptide of
SEQ ID NO: 14 are taught in the prior art by Young (a variant having 92.5%
homology) and Stanton (a variant having 96.7% identity), but does not teach
that the variants are overexpressed in colon, lung, or prostate tumor cells
(Answer 8-9). The Examiner also asserts, citing Haynes, 6 that even if the
amount of nucleic acid expressed from SEQ ID NO: 13 was overexpressed in
colon, lung, or prostate tumor cells, it does not necessarily follow that the
polypeptide of SEQ ID NO: 14 would also be overexpressed.
The amount of direction or guidance presented and the existence of working
examples: The Examiner states that, other than for the polypeptide of SEQ
ID NO: 14, the Specification fails to provide sufficient direction and/or
working examples to make those variants that have the same functions as
SEQ ID NO: 14, and that there are no examples of functional variants of
SEQ ID NO: 14 (Answer 9). The Examiner notes further that the
Specification does not teach which residues are critical to activity, and thus
which modifications will results in a variant having the same function as that
ofSEQIDNO:14. (A/, at 9-10.)

The relative skill of those in the art, the predictability or unpredictability of
the art, and the quantity of experimentation necessary: While
acknowledging that the level of skill in the art of DNA recombination
technology is relatively high, the Examiner states that procedures for making

6 Haynes et al. (Haynes), "Proteome analysis: Biological assay or data
archive," Electrophoresis, Vol. 19, pp. 1862-1871 (1998). The Examiner
cites Haynes for the proposition that "[t]he prior art teaches that the multi-
level control of protein synthesis and degradation in cells means that only
the direct analysis of mature protein products can reveal their correct
identities, their relevant state of modification and/or association and their
amounts" (Answer 9).

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variants of the polypeptide of SEQ ID No: 14 as set forth by the claims that
still retain its activity are not conventional and are unpredictable. (Id. at 10.)
The Examiner concludes that "due to lack of the disclosure of the functions
of encompassed polypeptides structurally related to SEQ ID NO: 14, [lack
of] sufficient guidance and/or working examples provided in the
specification, and [lack of] teachings in the art on how to use those variants
of the polypeptide of SEQ ID NO: 14, it would take undue experimentation
for one skilled in the art to make and use the variants of polypeptide of SEQ
ID NO: 14." (Mat 10-11.)

Appellants argue that "the claimed variants all share the functional
limitation that 'the nucleic acid encoding said polypeptide is overexpressed
in colon, lung or prostate tumor cells," and that Example 30 of the
Specification provides step-by-step guidelines and protocols for the
microarray analysis (Br. 28 (emphasis in original)). Appellants assert
further that "[t]he specification provides detailed guidance as to changes that
may be made to a PRO polypeptide without adversely affecting its activity
(page 81, line 17, to page 83, line 26)" (Br. 29).

Appellants submit

that the specification provides ample guidance such that one of
skill in the art could readily test the nucleic acid encoding a
variant polypeptide to determine whether it is overexpressed in
colon, lung or prostate tumors by the methods set forth in
Example 30. Furthermore, one of ordinary skill in the art has a
sufficiently high level of technical competence to identify
sequences with at least 80% identity to SEQ ID NO: 14.
Accordingly, one of ordinary skill could practice the claimed
invention without undue experimentation.

The claims currently recite polypeptide sequences
associated with a specific biological activity of the encoding
nucleic acid. This biological activity together with the well

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defined relatively high degree of sequence identity and general
knowledge in the art at the time the invention was made,
sufficiently defines the claimed genus such that, one skilled in
the art, at the effective date of the present application, would
have known how to make and use the claimed polypeptide
sequences without undue experimentation.

(Id.)

As noted with respect to the utility rejection, Table 8 of the
Specification states that PR01886 is overexpressed in colon tumor, prostate
tumor, and lung tumor, as compared to universal normal control.
(Specification 135.)

Page 81, line 17 to page 83, line 26 of the Specification provides
general guidance as to the generation of PRO polypeptide variants, which
guidance is applicable to the generation of any polypeptide variant. The
Specification does not disclose any guidance that is specific to the PRO 1866
(SEQ ID NO: 14) polypeptide. The Specification also does not present any
data as to the biological function of PRO 1866 other than the microarray data
that demonstrates that it may be used as a tumor marker.

PRINCIPLES OF LAW

Enablement is a question of law, based on underlying findings of fact.
See, e.g., In re Wands, 858 F.2d 731, 735, 8 USPQ2d 1400, 1402
(Fed. Cir. 1988). "When rejecting a claim under the enablement
requirement of section 112, the PTO bears an initial burden of setting forth a
reasonable explanation as to why it believes that the scope of protection
provided by that claim is not adequately enabled by the description of the

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invention provided in the specification of the application." In re Wright, 999
F.2d 1557, 1561-62, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).

"[T]o be enabling, the specification . . . must teach those skilled in the
art how to make and use the full scope of the claimed invention without
'undue experimentation.'" Wright, 999 F.2d at 1561, 27 USPQ2d at 1513
(emphasis added), quoted in Genentech, Inc. v. Novo Nordisk, A/S, 108 F.3d
1361, 1365, 42 USPQ2d 1001, 1004 (Fed. Cir. 1997). Thus, "there must be
sufficient disclosure, either through illustrative examples or terminology, to
teach those of ordinary skill how to make and how to use the invention as
broadly as it is claimed." In re Vaeck, 947 F.2d 488, 496 & n. 23, 20
USPQ2d 1438, 1445 & n. 23 (Fed. Cir. 1991), quoted in Enzo Biochem, Inc.
v. Calgene, Inc., 188 F.3d 1362, 1372, 52 USPQ2d 1 129, 1 138 (Fed. Cir.
1999).

"Patent protection is granted in return for an enabling disclosure
not for vague intimations of general ideas that may or may not be workable."
Genentech, 108 F.3d at 1365, 42 USPQ2d at 1005. "Tossing out the mere
germ of an idea does not constitute enabling disclosure. While every aspect
of a generic claim certainly need not have been carried out by an inventor, or
exemplified in the specification, reasonable detail must be provided in order
to enable members of the public [skilled in the art] to understand and carry
out the invention." Id. at 1366, 42 USPQ2d at 1005 (emphasis added).

ANALYSIS

While Appellants have demonstrated that the polypeptide of SEQ ID
NO: 14 is a diagnostic marker for colon, lung, and prostate cancer, the
Specification sets forth no biological activity or function for the protein. All

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that is disclosed is the sequence information for SEQ ID NO: 14. Moreover,
the Specification does not disclose which portions of the polypeptide of SEQ
ID NO: 14 are required for activity, and which regions are tolerant to
substitution. With respect to the variants, all that is disclosed by the
Specification are methods of making polypeptide variants in general, and
information as to what amino acid substitutions are generally considered by
the skilled artisan to be conservative. The Specification, however, does not
disclose any guidance of generating variants of the polypeptide of SEQ ID
NO: 14 that is specific to SEQ ID NO: 14, wherein the variant is
overexpressed in colon, lung, or prostate tumor cells.

Without information as to the biological activity or function, it would
be unpredictable to the skilled artisan which variants of SEQ ID NO: 14
would also perform as a diagnostic marker for colon, lung, and prostate
cancer. Claim 72 is drawn to variants having 80% amino acid sequence
identity, but, as noted by the Examiner, two variants of the polypeptide of
SEQ ID NO: 14 having higher sequence identity have been disclosed by
Young (a variant having 92.5% homology) and by Stanton (a variant having
96.7% identity), but have not been shown to be overexpressed in colon,
lung, or prostate tumor cells.

Given the lack of guidance as to the biological function or activity of
the polypeptide of SEQ ID NO: 14, and the lack of guidance as to those
variants of SEQ ID NO: 14 that would be expected to also perform as a
diagnostic marker for colon, lung, and prostate cancer, as well as the
enormous number of variants that would have 80% sequence identity with

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SEQ ID NO: 14, 7 it would require an undue amount of experimentation by
one skilled in the art to use the full scope of variants encompassed by claim
72 without further guidance from Appellants.

CONCLUSIONS OF LAW

We conclude that the Specification does not enable one skilled in the
art to use the full scope of the PRO 1866 (SEQ ID NO: 14) variants of claim
72 without an undue amount of experimentation, and the rejection is
affirmed.

WRITTEN DESCRIPTION

ISSUE

The Examiner contends that the claims are drawn to an isolated
polypeptide having 80%, 85%, 90%, 95%, and 99% sequence identity to
SEQ ID NO: 14, and due to the breadth of the claimed genus and the lack of
definitive structural or functional features of the claimed genus, one skilled
in the art would not recognize from the disclosure that the Appellants were
in possession of the claimed genus

Appellants contend that the genus of polypeptides with at least 80%
sequence identity to SEQ ID NO: 14, which possess the functional property
of having a nucleic acid which is overexpressed in colon, lung or prostate
tumors, would meet the requirement of 35 U.S.C. § 1 12, first paragraph, as
providing adequate written description.

7 The polypeptide of SEQ ID NO: 14 is 541 amino acids long, and as there
are 20 naturally occurring peptides, the number of variants that would have
80%o sequence identity to SEQ ID NO: 14 would be enormous.

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Thus, the issue is does the disclosure as filed provide adequate written
description to support the genus of variants of the polypeptide of SEQ ID
NO: 14 encompassed by claim 72?

FACTS

The Examiner rejected claims 72-76, 83, and 84 under 35 U.S.C. §
112, first paragraph, as containing subject matter that was not described in
the specification in such a way as to reasonably convey to one skilled in the
relevant art that the inventors, at the time the application was filed, had
possession of the claimed invention (Answer 1 1).

As we find that Appellants do not argue the claims separately, we
focus our attention on independent claim 72. 37 C.F.R. § 41.37(c)(l)(vii)
(2006).

The Examiner notes that the claims are drawn to an isolated

polypeptide having 80%, 85%, 90%, 95%, and 99% sequence identity to

SEQ ID NO: 14, asserting that the claims do not require that the polypeptide

have any particular conserved structure or any other distinguishing feature.

(Answer 12.) According to the Examiner,

[wjhile the claims recite a limitation "wherein the nucleic acid
encoding said polypeptide is overexpressed in colon, lung or
prostate tumor cells," such a limitation does not limit the scope
of the invention in actuality because the specification does not
reasonably identify or confirm that the polypeptide or the
nucleic acid encoding the polypeptide is overexpressed in
colon, lung or prostate tumor cells. Thus, the claims are drawn
to a genus of polypeptides that is defined only by a partial
structure in the form of a recitation of percent identity.

(Id.)

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Moreover, according to the Examiner, the disclosure of SEQ ID
NO: 14 and its encoding nucleic acid sequence, SEQ ID NO: 13, "does not
adequately support the scope of the claimed genus, which encompasses a
substantial variety of homologues or variants of the polypeptide of SEQ ID
NO: 14." (Id.) The disclosure as filed, the Examiner asserts, fails to provide
sufficient description as to structural and functional features of the claimed
genus, such as conserved regions that are critical to the structure and
function of the genus claimed. (Id. at 13.) Thus, "[t]here is no description
of the sites at which variability may be tolerated and there is no information
regarding the relation of structure to function." (Id.)

The Examiner concludes:

Due to the breadth of the claimed genus and lack of the
definitive structural or functional features of the claimed genus,
one skilled in the art would not recognize from the disclosure
that the Appellant was in possession of the claimed genus.
Accordingly, only the isolated polypeptide comprising SEQ ID
NO: 14 . . ., but not the full breadth of the claims meets the
written description provision of 35 U.S.C. § 1 12, first
paragraph.

(Id. at 13-14.)

Appellants assert that "the genus of polypeptides with at least 80%
sequence identity to SEQ ID NO: 14, which possess the functional property
of having a nucleic acid which is overexpressed in colon, lung or prostate
tumors would meet the requirement of 35 U.S.C. § 1 12, first paragraph, as
providing adequate written description." (Br. 32.) According to Appellants,
the level of skill in the art of recombinant DNA technology is high, and thus
"the teachings imparted in the specification must be evaluated through the
eyes of a highly skilled artisan as of the date the invention was made." (Id.)

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Appellants argue further that Example 30 provides step-by-step
guidelines and protocols for performing the microarray analysis, thus the
skilled artisan could test variants of the PR01866 polypeptide (SEQ ID
NO: 14) to determine if they are overexpressed in colon, lung, or prostate
rumor cells. (Id.) Moreover, Appellants aver, the Specification (page 81,
line 17, to page 83, line 26) provides detailed guidance as to what changes
may be made to the PRO polypeptide without affecting its activity, such as
exemplary and preferred amino acid substitutions (Br. 33). "Accordingly,"
Appellants assert, "one of skill in the art could identify whether a variant
PRO 1 866 sequence falls within the parameters of the claimed invention."
(Id.).

Appellants note that factors to be considered in evidencing possession
of a claimed genus include structural features and functional activity, which
they assert they have provided by reciting a structural feature — 80%
sequence identity to SEQ ID NO: 14 — as well as a specific functional
activity for the encoding nucleic acids. (Id.)

As noted above with respect to the enablement rejection, page 81, line
17 to page 83, line 26 of the Specification provides general guidance as to
the generation of PRO polypeptide variants. The Specification does not
disclose any guidance that is specific to the PRO 1866 (SEQ ID NO: 14)
polypeptide. The Specification also does not present any data as to the
biological function of PRO 1866 other than the microarray data that
demonstrates that it may be used as a tumor marker.

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PRINCIPLES OF LAW

The requirement for written description under the first paragraph of
section 1 12 is separate and distinct from the enablement requirement of that
paragraph. See Vas-Cathlnc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19
USPQ2d 1111,1116-17 (Fed. Cir. 1991). Compliance with the written
description requirement is a question of fact. Id.

"A written description of an invention involving a chemical genus,
like a description of a chemical species, 'requires a precise definition, such
as by structure, formula, [or] chemical name,' of the claimed subject matter
sufficient to distinguish it from other materials." University of California v.
Eli Lilly and Co., 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1405 (Fed. Cir.
1997 (bracketed material in original). The claims in Lilly were directed
generically to vertebrate or mammalian insulin cDNAs. See id. at 1567,
43 USPQ2d at 1405. The court held that a structural description of a rat
cDNA was not an adequate description of these broader classes of cDNAs.

The Lilly court explained that

a generic statement such as. . . 'mammalian insulin cDNA,'
without more, is not an adequate written description of the
genus because it does not distinguish the claimed genus from
others, except by function. It does not specifically define any
of the genes that fall within its definition. It does not define
any structural features commonly possessed by members of the
genus that distinguish them from others. One skilled in the art
therefore cannot, as one can do with a fully described genus,
visualize or recognize the identity of the members of the genus.

Id. at 1568, 43 USPQ2d at 1406. Finally, the Lilly court set out exemplary

ways in which a genus of cDNAs could be described:

A description of a genus of cDNAs may be achieved by means
of a recitation of a representative number of cDNAs, defined by

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nucleotide sequence, falling within the scope of the genus or of
a recitation of structural features common to the members of the
genus, which features constitute a substantial portion of the
genus.

Mat 1569.

Our appellate reviewing court revisited the issue of describing DNA.
See Enzo Biochem, Inc. v. Gen-Probe Inc., 296 F.3d 1316, 63 USPQ2d 1609
(Fed. Cir. 2002). The Enzo court held that a claimed DNA could be
described without, necessarily, disclosing its structure. The court adopted
the standard that "the written description requirement can be met by
'show[ing] that an invention is complete by disclosure of sufficiently
detailed, relevant identifying characteristics . . . i.e., complete or partial
structure, other physical and/or chemical properties, functional
characteristics when coupled with a known or disclosed correlation between
function and structure, or some combination of such characteristics.'" See
id. at 1324, 63 USPQ2d at 1613 (emphasis omitted, ellipsis and bracketed
material in original).

Our appellate review court has also noted that "Eli Lilly did not hold
that all functional descriptions of genetic material necessarily fail as a matter
of law to meet the written description requirement; rather, the requirement
may be satisfied if in the knowledge of the art the disclosed function is
sufficiently correlated to a particular, known structure." Amgen, Inc. v.
Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1332, 65 USPQ2d 1385, 1398
(Fed. Cir. 2003).

This standard applies to polypeptides as well as DNAs. See
University of Rochester v. G.D. Searle & Co., Inc., 358 F.3d 916, 925, 69
USPQ2d 1886, '893 (Fed. Cir. 2004); "We agree with Rochester that Fiers,

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Lilly, and Enzo differ from this case in that they all related to genetic
material whereas this case does not, but we find that distinction to be
unhelpful to Rochester's position. It is irrelevant; the statute applies to all
types of inventions. We see no reason for the rule to be any different when
non-genetic materials are at issue."

With respect to the use of an assay to support written description, in
University of Rochester, the patent claimed a method of selectively
inhibiting the enzyme PGHS-2 (also known as COX-2) by "administering a
non-steroidal compound that selectively inhibits activity of the PGHS-2 gene
product in a human." Id. at 918, 69 USPQ2d at 1888. The patent "described
in detail how to make cells that express either COX-1 or COX-2, but not
both . . . , as well as 'assays for screening compounds, including peptides,
polynucleotides, and small organic molecules to identify those that inhibit
the expression or activity of the PGHS-2 gene product.f']" Id. at 927, 69
USPQ2d at 1895.

The court held that the disclosure of screening assays and general
classes of compounds was not adequate to describe compounds having the
desired activity: without disclosure of which peptides, polynucleotides, or
small organic molecules have the desired characteristic, the claims failed to
meet the description requirement of § 112. See id. ("As pointed out by the
district court, the '850 patent does not disclose just 'which "peptides,
polynucleotides, and small organic molecules" have the desired
characteristic of selectively inhibiting PGHS-2.' . . . Without such
disclosure, the claimed methods cannot be said to have been described.").

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ANALYSIS

We find that the disclosure as filed does not provide adequate written
description to support the genus of variants of the polypeptide of SEQ ID
NO: 14 encompassed by claim 72, and the rejection is affirmed.

Claim 72 is drawn to variants that have 80% sequence identity to SEQ
ID NO: 14, wherein the nucleic acid encoding said polypeptide is
overexpressed in colon, lung or prostate tumor cells. The Specification does
not disclose a biological function or activity of the polypeptide of SEQ ID
NO: 14, and also does not disclose a single variant that also performs as a
diagnostic marker for colon, lung, and prostate cancer. Thus, the genus
encompasses an enormous number of sequences, but the Specification only
describes a single member of that genus — SEQ ID NO: 14.

In addition, there is no disclosure of sufficiently detailed, relevant
identifying characteristics, such as other physical and/or chemical properties,
or functional characteristics, that when coupled with a known or disclosed
correlation between function and structure (i.e., the sequence), or some
combination of such characteristics, would constitute an adequate written
description of the claimed invention. All that is disclosed is the amino acid
sequence and that it may be used as a diagnostic marker for certain tumor
types. While the skilled artisan may be able to determine polypeptides that
have 80% sequence identity with SEQ ID NO: 14, without any disclosure of
function or what residues are required for the polypeptide to function as a
diagnostic marker, the skilled artisan cannot, as one can do with a fully
described genus, visualize or recognize the identity of the members of the
genus that would be useful as a diagnostic marker.

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Moreover, just as in the University of Rochester case, discussed
above, the present application discloses a broad genus of chemical
compounds (polypeptides having 80% sequence identity to SEQ ID NO: 14)
but the claims are limited to only those compounds having a desired
characteristic (wherein the nucleic acid encoding said polypeptide is
overexpressed in colon, lung, or prostate tumor cells). Just as in University
of Rochester, the present specification does not disclose which nucleic acids
encoding the many possible polypeptides having 80% sequence identity to
SEQ ID NO: 14 are overexpressed in colon, lung, or prostate tumor cells.

Granted, those skilled in the art could screen libraries of naturally
occurring DNAs for overexpression in colon, lung or prostate tumor cells to
identify for themselves specific DNAs that encode polypeptides having 80%
sequence identity to SEQ ID NO: 14. That, however, does not make up for
the deficiency of the specification's description. The University of
Rochester court specifically noted that the patent at issue there disclosed
screening assays to identify compounds having the desired characteristic, but
nonetheless held that the description was inadequate. The same holds true
here.

PRIOR ART

ISSUE

The Examiner contends that claims 72-74, 83, and 84 are anticipated
by Young, and that claims 72-75, 83, and 84 are anticipated by Stanton.

Appellants contend that have demonstrated invention prior to the
effective filing dates of Young and Stanton, and thus Young and Stanton are
not anticipatory art within the meaning of 35 U.S.C. § 102(e).

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Thus, the issue is whether the Declaration submitted under 37 C.F.R.
§ 1.131 is sufficient to overcome the rejections over the prior art made under
35 U.S.C. § 102(e)?

FACTS

The Examiner rejected claims 72-74, 83, and 84 under 35 U.S.C.
§ 102(e) as being anticipated by Young (Answer 14).

According to the Examiner, Young teaches a polypeptide that shares
92.5% sequence identity with SEQ ID NO: 14. (Id.)

The Examiner rejected claims 72-75, 83, and 84 under 35 U.S.C.
§ 102(e) as being anticipated by Stanton. (Id. at 15.)

According to the Examiner, Stanton teaches a polypeptide that shares
96.7% sequence identity with SEQ ID NO: 14. (Id.)

Appellants do not argue the merits of the rejections. Rather,
Appellants assert that the declaration submitted under 37 C.F.R. § 1.13 1 is
sufficient to show invention prior to the effective filing dates of Young and
Stanton (Br. 34).

Appellants cite the 37 C.F.R. § 1.131 Declaration of Dr. Goddard, Dr.
Godawski, Dr. Gurney, Dr. Smith, and Dr. Wood, to support the proposition
that the inventors "conceived and reduced to practice the PRO 1866
polypeptide and its encoding nucleic acid sequence in the United States prior
to December 4, 1998." (Id. (emphasis removed).) According to Appellants,
"the Declaration clearly establishes that the claimed polypeptides and the
nucleic acids encoding them, were conceived and reduced to practice prior
to December 4, 1998, and that the differential expression of PRO 1866 in the

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multiple types of cancer cells based on microarray analysis were
demonstrated prior to March 3 1 , 2000." (Id. at 35.)

Appellants cite MPEP § 715.03 for the proposition that:

proof of prior completion of a species different from the
reference species will be sufficient to overcome a reference
indirectly under 37 C.F.R. § 1.131 if the reference species
would have been obvious in view of the species shown to have
been made by applicants. Alternatively, the applicant may be
able to antedate the reference indirectly by demonstrating
possession of the claimed genus prior to the reference date.
The test is whether the species completed by applicant prior to
the reference date provided an adequate basis for inferring that
the invention has generic applicability. . . . The test is whether
the facts set out in the affidavit are such as would persuade one
skilled in the art that the applicant possessed so much of the
invention as is shown in the reference. In re Schaub, 537 F.2d
509, 190U.S.P.Q. 324(C.C.P.A. 1976).

(Br. at 35-36 (footnote omitted) (emphasis in original)).

Appellants cite their arguments regarding the written description
rejection, asserting that the "disclosed polypeptide of SEQ ID NO[:]14 is
representative for a genus encompassing its variants." (Id. at 36.)

Appellants also cite Example 14 of the Synopsis of Application of
Written Description Guidelines issued by the USPTO, which Appellants
note states

that protein variants meet the requirements of 35 U.S.C. § 1 12,
first paragraph, as providing adequate written description for
the claimed invention even if the specification contemplates but
does not exemplify variants of the protein if (1) the procedures
for making such variant proteins are routine in the art, (2) the
specification provides an assay for detecting the functional
activity of the protein and (3) the variant proteins possess the

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specified functional activity and at least 95% sequence identity
to the reference sequence.

(Br. 36.)

The Declaration submitted under 37 C.F.R. § 1.131 of Dr. Audrey
Goddard, Dr. Paul J. Godowski, DR. Austin Gurney, Dr. Victoria Smith, and
Dr. William I. Wood, dated October 26, 2004, states at 1J10 that "[b]oth the
DNA-44174 and the PRO 1866 polypeptide sequences were obtained prior to
December 4, 1998." It further states at ^17 that "the microarray analysis of
mRNA expression of PRO 1866 in cancer cells was conducted prior to
March 31, 2000, and the data indicate that the mRNA of PRO 1866 is
overexpressed in colon, lung, and prostate tumors."

PRINCIPLES OF LAW

A declaration under 37 C.F.R. § 1.131 must establish possession of
either the whole invention claimed or of something falling within the claim
such as a species of a claimed genus, such that the claim as a whole reads on
it. See In re Tanczyn, 347 F.2d 830, 831-32, 146 USPQ 298, 300 (CCPA
1965); see also MPEP § 715.02

Where the disclosure in the prior art is only a single species of a genus
claim, appellant can overcome the rejection through the use of a 13 1
declaration by showing prior possession of the species disclosed in the
reference. In re Stempel, 241 F.2d 755, 759, 113 USPQ 77, 81 (CCPA
1957). If the species disclosed in the reference is different from the species
that was disclosed in the 131 declaration, the 131 declaration can only
overcome the reference if the species shown in the reference would have
been obvious in view of the species shown to have been made by appellant.

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See In re Clarke, 356 F.2d 987, 961, 148 USPQ 665, 668-69 (CCPA 1966).
If appellant cannot show possession of the species of the reference, appellant
may be able to antedate the reference by showing prior completion of one or
more species such that appellant was in possession of the claimed genus.
See id. Note it is not necessary that the evidence demonstrate that appellant
viewed the invention as encompassing more than the species actually made,
only that the evidence would persuade one skilled in the art that appellant
possessed so much of the invention as is shown in the reference. In re
Schaub, 537 F.2d 509, 512 131, 190 USPQ 324, 326 (CCPA 1976). See
also M?E? 715.03.

ANALYSIS

The species disclosed by the Declaration submitted under 131 is
different than that disclosed by either the Young or Stanton reference. In
addition, we have already determined in reviewing the rejection under
35 U.S.C. § 1 12, first paragraph, for written description, that the disclosure
of a single species, i.e., the polypeptide of SEQ ID NO: 14 does not
demonstrate that Appellants had possession of the claimed genus. Thus, we
need to determine if the species disclosed by Young and Stanton would be
obvious over the polypeptide of SEQ ID NO: 14.

Appellants' claim 72 is drawn to a polypeptide having 80% sequence
identity to SEQ ID NO: 14. Thus, the species of Young and Stanton are
clearly encompassed by the claims. Moreover, Appellants disclose that the
polypeptide is overexpressed in colon, lung or prostate tumor cells. As we
have already found above, however, neither the Declaration nor the
disclosure as filed provides guidance as to what regions are necessary for

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activity, or what the biological activity is, other than its use as a diagnostic
marker. Thus, we conclude that there is nothing in the Declaration or the
disclosure as filed that would suggest to one of ordinary skill in the art the
species disclosed by Young and Stanton, and thus that the polypeptide of
SEQ ID NO: 14 does not render obvious the species disclosed by Young and
Stanton. See In re Baird, 16 F.3d 380, 382, 29 USPQ2d 1550, 1552 (Fed.
Cir. 1994) ("The fact that a claimed compound may be encompassed by a
disclosed generic formula does not by itself render that compound
obvious.").

Thus, as the Declaration submitted under 37 C.F.R. § 1.131 is not
sufficient to overcome the rejections over the prior art made under
35 U.S.C. § 102(e), the rejections of claims 72-74, 83, and 84 under 35
U.S.C. § 102(e) as being anticipated by Young, and claims 72-75, 83, and 84
under 35 U.S.C. § 102(e) as being anticipated by Stanton, are affirmed.

CONCLUSION

In summary, we reverse the rejection of claims 72-79 and 82-84 under 35
U.S.C. § 101 as not being supported by either a specific and substantial
utility or a well-established utility. We do, however, affirm the rejection of
claims 72-76, 83, and 84 under 35 U.S.C. § 1 12, first paragraph, as not being
enabled by the specification; the rejection claims 72-76, 83 and 84 under 35
U.S.C. § 1 12, first paragraph, as lacking adequate written description; the
rejection of claims 72-74, 83 and 84 stand rejected under 35 U.S.C. § 102(e)
as being anticipated by Young; and the rejection of claims 72-75, 83 and 84
under 35 U.S.C. § 102(e) as being anticipated by Stanton.

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AFFIRMED-IN-PART

lbg

Ginger R. Dreger
Knobbe Martens Olson & Bear
201 California Street, Suite 1150
San Francisco CA94111

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